ApoC-III gene polymorphisms and risk of coronary artery disease

Abstract

Several polymorphisms in the apolipoprotein C-III (apoC-III) gene have been associated with hypertriglyceridemia, but the link with coronary artery disease risk is still controversial. In particular, apoC-III promoter sequence variants in the insulin responsive element (IRE), constitutively resistant to downregulation by insulin, have never been investigated in this connection. We studied a total of 800 patients, 549 of whom had angiographically documented coronary atherosclerosis, whereas 251 had normal coronary arteriograms. We measured plasma lipids, insulin, apoA-I, apoB, and apoC-III and assessed three polymorphisms in the apoC-III gene, namely, T-455C in the IRE promoter region, C1100T in exon 3, and Sst1 polymorphic site (S1/S2) in the 3 untranslated region. Each variant influenced triglyceride levels, but only the T-455C (in homozygosity) and S2 alleles influenced apoC-III levels. In coronary artery disease (CAD) patients, 18.6% were homozygous for the ؊ 455C variant compared with only 9.2% in CAD-free group ( P Ͻ 0.001). In logistic regression models, homozygosity for ؊ 455C variant was associated with a significantly increased risk of CAD (OR ‫؍‬ 2.5 and 2.18 for unadjusted and adjusted models, respectively) suggesting that it represents an independent genetic susceptibility factor for CAD. -

Apolipoprotein C-III, n-3 Polyunsaturated Fatty Acids, and “Insulin-Resistant” T−455C APOC3 Gene Polymorphism in Heart Disease Patients: Example of Gene-Diet Interaction

“…The details of the study have been reported previously (16 ). Briefly, we selected a total of 848 unrelated adult patients of both sexes who were recruited consecutively from those referred to the Institute of Cardiovascular Surgery or to the Cardiovascular-Hypertension Unit of the Department of Internal Medicine of the University of Verona in Italy and underwent coronary angiography (the Verona Heart Project).…”

“…Serum lipids and the other common biochemical indices were measured as described previously (16 ). Apo A1, apo B, and apo E were measured by commercially available nephelometric immunoassays; antisera, calibrators, and the BNII nephelometer were from Dade Behring.…”

“…Recently we reported that the TϪ455C variant on the APOC3 gene promoter is associated with increased TG and apo C-III concentrations (16,17 ) and represents an independent susceptibility factor for CAD (16 ), particularly in the presence of metabolic syndrome (17 ). However, in patients with high dietary intake, n-3 PUFAs could act as mediating factors able to substantially reduce the "over time impact" of APOC3 gene variants.…”

Using primary murine intestinal enteroids to study dietary TAG absorption, lipoprotein synthesis, and the role of apoC-III in the intestine

“…In plasma, apoC-III resides on both TAGrich lipoproteins and HDLs. Overproduction of apoC-III and TAG-rich lipoproteins is a common feature in patients with hypertriglyceridemia (10,11). apoC-III also stimulates hepatic synthesis and secretion of VLDLs (12,13).…”

Frequencies of the T-455C and C-482T apoCIII gene polymorphisms in different South African population groups and their relationship to fasting serum triglyceride levels

“…(9)(10)(11) Olivieri and co-workers, (5) identifi ed apoCIII polymorphisms that are believed to play an important role in the metabolism of circulating triglyceride rich lipoproteins. Several variant alleles of the apoCIII gene have been investigated as possible genetic markers of hypertriglyceridaemia.…”